Article ID Journal Published Year Pages File Type
8633220 Neuropeptides 2018 28 Pages PDF
Abstract
Migraine is a condition without apparent pathology. Its cardinal symptom is the prolonged excruciating headache. Theories about this pain have posited pathologies which run the gamut from neural to vascular to neurovascular, but no observations have detected a plausible pathology. We believe that no pathology can be found for migraine headache because none exists. Migraine is not driven by pathology - it is driven by neural events produced by triggers - or simply by neural noise- noise that has crossed a critical threshold. If these ideas are true, how does the pain arise? We hypothesise that migraine headache is a consequence of withdrawal of descending pain control, produced by “noise” in the cerebral cortex. Nevertheless, there has to be a neural circuit to transform cortical noise to withdrawal of pain control. In our hypothesis, this neural circuit extends from the cortex, synapses in two brainstem nuclei (the periaqueductal gray matter and the raphe magnus nucleus) and ultimately reaches the first synapse of the trigeminal sensory system. The second stage of this circuit uses serotonin (5HT) as a neurotransmitter, but the neuronal projection from the cortex to the brainstem seems to involve relatively uncommon neurotransmitters. We believe that one of these is somatostatin (SST). Temporal changes in levels of circulating SST mirror the temporal changes in the incidence of migraine, particularly in women. The SST2 receptor agonist octreotide has been used with some success in migraine and cluster headache. A cortical to PAG/NRM neural projection certainly exists and we briefly review the anatomical and neurophysiological evidence for it and provide preliminary evidence that SST may the critical neurotransmitter in this pathway. We therefore suggest that the withdrawal of descending tone in SST-containing neurons, might create a false pain signal and hence the headache of migraine.
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